The broad objectives in further clarifying the nature of the platelet defects in a variety of patients with bleeding disorders shall be to (1) determine the mechanism that accounts for our recent findings of a decreased synthesis of platelet prostaglandins in storage pool disease (SPD), (2) obtain further information on a possible defect in the release mechanism in SPD by studying the content and release of lysosomal enzymes, (3) perform subcellular fractionation studies to determine if the dense storage granules are absent or functionally deficient in SPD, (4) extend recent studies that suggest an increased metabolism of serotonin in SPD, (5) determine whether the storage-pool deficiency in the platelets of the Fawn-Hooded rat is the result of an abnormality acquired during thrombopoeisis or after release into the circulation, (6) further define the molecular defects in von Willebrand's disease (VWD) that account for deficiencies of AHF procoagulant activity and antigen, and a high molecular weight "von Willebrand" factor (VWF) necessary for normal platelet function (assayed by the method of ristocetin-induced platelet aggregation), (7) determine if the plasma of patients with VWD show decreased binding of low molecular weight AHF (resulting in increased lability of the latter) due to deficiency of a high molecular carrier having VWF activity, (8) determine if the VWF can correct the defect we have recently found in the adhesion of von Willebrand platelets to subendothelium, (9) determine the nature of the subendotheial component to which platelets in von Willebrand's disease fail to adhere, and (10) study possible defects in adhesion/aggregation to subenodothelium in patients with SPD, aspirin-like defects, thrombasthenia, and the Bernard-Soulier syndrome under flow conditions (Baumgartner technique) approximating those in vivo.